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https://www.readbyqxmd.com/read/28344863/tumor-infiltrating-lymphocytes-tils-from-patients-with-glioma
#1
Zhenjiang Liu, Qingda Meng, Jiri Bartek, Thomas Poiret, Oscar Persson, Lalit Rane, Elena Rangelova, Christopher Illies, Inti Harvey Peredo, Xiaohua Luo, Martin Vijayakumar Rao, Rebecca Axelsson Robertson, Ernest Dodoo, Markus Maeurer
Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28316990/diagnostic-and-therapeutic-biomarkers-in-glioblastoma-current-status-and-future-perspectives
#2
REVIEW
Wojciech Szopa, Thomas A Burley, Gabriela Kramer-Marek, Wojciech Kaspera
Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3-5% of them survive for more than 5 years. The current GBM treatment standards include maximal resection followed by radiotherapy with concomitant and adjuvant therapies. Despite these aggressive therapeutic regimens, the majority of patients suffer recurrence due to molecular heterogeneity of GBM. Consequently, a number of potential diagnostic, prognostic, and predictive biomarkers have been investigated...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28302023/anti-egfrviii-chimeric-antigen-receptor-modified-t-cells-for-adoptive-cell-therapy-of-glioblastoma
#3
Pei-Pei Ren, Ming Li, Tian-Fang Li, Shuang-Yin Han
Glioblastoma (GBM) is one of the most devastating brain tumors with poor prognosis and high mortality. Although radical surgical treatment with subsequent radiation and chemotherapy can improve the survival, the efficacy of such regimens is insufficient because the GBM cells can spread and destroy normal brain structures. Moreover, these non-specific treatments may damage adjacent healthy brain tissue. It is thus imperative to develop novel therapies to precisely target invasive tumor cells without damaging normal tissues...
March 16, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28296511/targeted-delivery-of-doxorubicin-into-tumor-cells-by-nanostructured-lipid-carriers-conjugated-to-anti-egfrviii-monoclonal-antibody
#4
Saeideh Abdolahpour, Tayebeh Toliyat, Kobra Omidfar, Helmout Modjtahedi, Albert J Wong, Mohammad Javad Rasaee, Susan Kashanian, Maliheh Paknejad
Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the EGF receptor in many human tumors. This variant is tumor specific and highly immunogenic, thus, it can be used as a target for targeted drug delivery toward tumor cells. The major aim of this study was to develop an EGFRvIII-mediated drug delivery system by anti-EGFRvIII monoclonal antibody (MAb) conjugated to doxorubicin (Dox)-loaded nanostructured lipid carriers (NLC) to enhance the targeting specificity and cytotoxic effect of Dox on EGFRvIII-overexpressing cell line...
March 15, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28274144/prospect-of-rindopepimut-in-the-treatment-of-glioblastoma
#5
Aladine A Elsamadicy, Pakawat Chongsathidkiet, Rupen Desai, Karolina Woroniecka, S Harrison Farber, Peter E Fecci, John H Sampson
Rindopepimut (CDX-110) is a peptide vaccine that targets epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific epitope expressed in the most common and lethal primary malignant neoplasm of the brain - glioblastoma (GBM). Areas covered: The EGFRvIII mutation introduces an 801 base pair in-frame deletion of the extracellular domain of the transmembrane tyrosine kinase, resulting in constitutive kinase activity, amplification of cell growth, and inhibition of apoptosis. Rindopepimut contains a 14mer amino acid peptide spanning the EGFRvIII mutation site that is conjugated to keyhole limpet hemocyanin (KLH)...
April 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28198167/signal-peptide-peptidase-encoded-by-hm13-contributes-to-tumor-progression-by-affecting-egfrviii-secretion-profiles-in-glioblastoma
#6
Jian-Wei Wei, Jin-Quan Cai, Chuan Fang, Yan-Li Tan, Kai Huang, Chao Yang, Qun Chen, Chuan-Lu Jiang, Chun-Sheng Kang
BACKGROUND AND AIMS: EGFRvIII is the most prevalent glioblastoma mutation, occurring in more than 25% of glioblastomas. EGFRvIII cells release microvesicles that contain proteins, miRNAs, and mRNAs that enhance the growth and survival of surrounding tumor cells. However, little is known about the maturation process and regulatory mechanisms of secreted vesicles in EGFRvIII cells. METHODS: Signal peptide peptidase (SPP) provides a fascinating mechanism for protein cleavage and subsequent dislocation in the endoplasmic reticulum transmembrane domain...
March 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28101463/development-of-a-novel-human-single-chain-antibody-against-egfrviii-antigen-by-phage-display-technology
#7
Leila Rahbarnia, Safar Farajnia, Hossein Babaei, Jafar Majidi, Bahman Akbari, Shiva Ahdi Khosroshahi
Purpose: EGFRvIII as the most common mutant variant of the epidermal growth factor receptor is resulting from deletion of exons 2-7 in the coding sequence and junction of exons 1 and 8 through a novel glycine residue. EGFRvIII is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. The aim of the present study was identification of a novel single chain antibody against EGFRvIII as a promising target for cancer therapy. Methods: In this study, a synthetic peptide corresponding to EGFRvIII protein was used for screening a naive human scFv phage library...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28081256/inhibition-of-acetyl-coa-carboxylase-1-acc1-and-2-acc2-reduces-proliferation-and-de-novo-lipogenesis-of-egfrviii-human-glioblastoma-cells
#8
Jessica E C Jones, William P Esler, Rushi Patel, Adhiraj Lanba, Nicholas B Vera, Jeffrey A Pfefferkorn, Cecile Vernochet
Tumor cell proliferation and migration processes are regulated by multiple metabolic pathways including glycolysis and de novo lipogenesis. Since acetyl-CoA carboxylase (ACC) is at the junction of lipids synthesis and oxidative metabolic pathways, we investigated whether use of a dual ACC inhibitor would provide a potential therapy against certain lipogenic cancers. The impact of dual ACC1/ACC2 inhibition was investigated using a dual ACC1/ACC2 inhibitor as well as dual siRNA knock down on the cellular viability and metabolism of two glioblastoma multiform cancer cell lines, U87 and a more aggressive form, U87 EGFRvIII...
2017: PloS One
https://www.readbyqxmd.com/read/28039367/efficacy-and-safety-results-of-abt-414-in-combination-with-radiation-and-temozolomide-in-newly-diagnosed-glioblastoma
#9
David A Reardon, Andrew B Lassman, Martin van den Bent, Priya Kumthekar, Ryan Merrell, Andrew M Scott, Lisa Fichtel, Erik P Sulman, Erica Gomez, JuDee Fischer, Ho-Jin Lee, Wijith Munasinghe, Hao Xiong, Helen Mandich, Lisa Roberts-Rapp, Peter Ansell, Kyle D Holen, Hui K Gan
BACKGROUND: The purpose of this study was to determine the maximum tolerated dose (MTD), recommended phase II dose (RPTD), safety, and pharmacokinetics of ABT-414 plus radiation and temozolomide in newly diagnosed glioblastoma. ABT-414 is a first-in-class, tumor-specific antibody-drug conjugate that preferentially targets tumors expressing overactive epidermal growth factor receptor (EGFR). METHODS: In this multicenter phase I study, patients received 0.5-3.2 mg/kg ABT-414 every 2 weeks by intravenous infusion...
December 29, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/28032593/the-impact-of-co-expression-of-wild-type-egfr-and-its-ligands-determined-by-immunohistochemistry-for-response-to-treatment-with-cetuximab-in-patients-with-metastatic-colorectal-cancer
#10
Said Khelwatty, Sharadah Essapen, Izhar Bagwan, Margaret Green, Alan Seddon, Helmout Modjtahedi
Anti-EGFR mAbs cetuximab and panitumumab are routinely used for the treatment of patients with KRAS-wild type metastatic colorectal cancer (mCRC). However, in some patients their efficacy remains modest and with no clear association between the EGFR protein expression determined by PharmDx™ kit, and response to anti-EGFR therapies. Therefore, we investigated the relative expression and predictive value of wild-type EGFR (wtEGFR), mutated EGFRvIII and EGFR ligand proteins in mCRC patients treated with cetuximab...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28031526/radiolabeled-novel-mab-4g1-for-immunospect-imaging-of-egfrviii-expression-in-preclinical-glioblastoma-xenografts
#11
Xujie Liu, Chengyan Dong, Jiyun Shi, Teng Ma, Zhongxia Jin, Bing Jia, Zhaofei Liu, Li Shen, Fan Wang
Epidermal growth factor receptor mutant III (EGFRvIII) is exclusively expressed in tumors, such as glioblastoma, breast cancer and hepatocellular carcinoma, but never in normal organs. Increasing evidence suggests that EGFRvIII has clinical significance in glioblastoma prognosis due to its enhanced tumorigenicity and chemo/radio resistance, thus the development of an imaging approach to early detect EGFRvIII expression with high specificity is urgently needed. To illustrate this point, we developed a novel anti-EGFRvIII monoclonal antibody 4G1 through mouse immunization, cell fusion and hybridoma screening and then confirmed its specificity and affinity by a serial of assays...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28029074/a-rational-approach-to-target-the-epidermal-growth-factor-receptor-in-glioblas
#12
Madan M Kwatra
Glioblastoma (GBM) is a deadly brain cancer, and all attempts to control it have failed so far. However, the future looks bright, as we now know the molecular landscape of GBM through the work of The Cancer Genome Atlas (TCGA) program. GBMs exhibit significant inter- and intra-tumoral heterogeneity, and to control this type of tumor, a personalized approach is required. One target, whose gene is amplified and mutated in a large number of GBMs, is the epidermal growth factor receptor (EGFR). But all attempts to target it have been unsuccessful...
December 26, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28013405/production-and-quality-control-assessment-of-a-glp-grade-immunotoxin-d2c7-scdsfv-pe38kdel-for-a-phase-i-ii-clinical-trial
#13
Vidyalakshmi Chandramohan, Charles N Pegram, Hailan Piao, Scott E Szafranski, Chien-Tsun Kuan, Ira H Pastan, Darell D Bigner
D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. Initial pre-clinical testing demonstrated the anti-tumor efficacy of D2C7-IT against orthotopic glioblastoma xenograft models expressing EGFRwt, EGFRvIII, or both EGFRwt and EGFRvIII. A good laboratory practice (GLP) manufacturing process was developed to produce sufficient material for a phase I/II clinical trial...
April 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28011764/inhibition-of-radiation-induced-glioblastoma-invasion-by-genetic-and-pharmacological-targeting-of-mda-9-syntenin
#14
Timothy P Kegelman, Bainan Wu, Swadesh K Das, Sarmistha Talukdar, Jason M Beckta, Bin Hu, Luni Emdad, Kristoffer Valerie, Devanand Sarkar, Frank B Furnari, Webster K Cavenee, Jun Wei, Angela Purves, Surya K De, Maurizio Pellecchia, Paul B Fisher
Glioblastoma multiforme (GBM) is an intractable tumor despite therapeutic advances, principally because of its invasive properties. Radiation is a staple in therapeutic regimens, although cells surviving radiation can become more aggressive and invasive. Subtraction hybridization identified melanoma differentiation-associated gene 9 [MDA-9/Syntenin; syndecan-binding protein (SDCBP)] as a differentially regulated gene associated with aggressive cancer phenotypes in melanoma. MDA-9/Syntenin, a highly conserved double-PDZ domain-containing scaffolding protein, is robustly expressed in human-derived GBM cell lines and patient samples, with expression increasing with tumor grade and correlating with shorter survival times and poorer response to radiotherapy...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28004613/the-role-of-egfr-met-interactions-in-the-pathogenesis-of-glioblastoma-and-resistance-to-treatment
#15
Gao Guo, Ram N Narayan, Lindsay Horton, Toral R Patel, Amyn A Habib
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. It is a devastating and intractable disease with a poor outcome. Aberrant receptor tyrosine kinase signaling is a key driver in gliomagenesis and resistance to treatment. EGFR gene amplification and mutations are an important genetic alteration in GBM resulting in increased expression of EGFR wild type (EGFRwt) as well as mutant oncogenic forms of the EGFR. EGFRvIII is the most common oncogenic mutant in GBM and is usually co-expressed with EGFRwt...
2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27998759/the-crispr-cas9-system-targeting-egfr-exon-17-abrogates-nf-%C3%AE%C2%BAb-activation-via-epigenetic-modulation-of-ubxn1-in-egfrwt-viii-glioma-cells
#16
Kai Huang, Chao Yang, Qi-Xue Wang, Yan-Sheng Li, Chuan Fang, Yan-Li Tan, Jian-Wei Wei, Yun-Fei Wang, Xin Li, Jun-Hu Zhou, Bing-Cong Zhou, Kai-Kai Yi, Kai-Liang Zhang, Jie Li, Chun-Sheng Kang
Worldwide, glioblastoma (GBM) is the most lethal and frequent intracranial tumor. Despite decades of study, the overall survival of GBM patients remains unchanged. epidermal growth factor receptor (EGFR) amplification and gene mutation are thought to be negatively correlated with prognosis. In this study, we used proteomics to determine that UBXN1 is a negative downstream regulator of the EGFR mutation vIII (EGFRvIII). Via bioinformatics analysis, we found that UBXN1 is a factor that can improve glioma patients' overall survival time...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27984065/isolation-and-characterization-of-a-novel-human-scfv-inhibiting-egfr-viii-expressing-cancers
#17
Leila Rahbarnia, Safar Farajnia, Hossein Babaei, Jafar Majidi, Hassan Dariushnejad, Mohammad Kazem Hosseini
EGFRvIII, a mutant form of epidermal growth factor receptor is highly expressed in glioblastoma, carcinoma of the breast, ovary, and lung but not in normal cells. This tumor specific antigen has emerged as a promising candidate for antibody based therapy of several cancers. The aim of the present study was isolation and characterization of a human single chain antibody against EGFRvIII as a promising target for cancer therapy. For this, a synthetic peptide corresponding to EGFRvIII protein was used for screening the naive human scFv phage library...
October 29, 2016: Immunology Letters
https://www.readbyqxmd.com/read/27886573/nuclear-transportation-of-exogenous-epidermal-growth-factor-receptor-and-androgen-receptor-via-extracellular-vesicles
#18
Jolene Read, Alistair Ingram, Hassan A Al Saleh, Khrystyna Platko, Kathleen Gabriel, Anil Kapoor, Jehonathan Pinthus, Fadwa Majeed, Talha Qureshi, Khalid Al-Nedawi
Epidermal growth factor receptor (EGFR) plays a central role in the progression of several human malignancies. Although EGFR is a membrane receptor, it undergoes nuclear translocation, where it has a distinct signalling pathway. Herein, we report a novel mechanism by which cancer cells can directly transport EGFR to the nucleus of other cells via extracellular vesicles (EVs). The transported receptor is active and stimulates the nuclear EGFR pathways. Interestingly, the translocation of EGFR via EVs occurs independently of the nuclear localisation sequence that is required for nuclear translocation of endogenous EGFR...
January 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/27883139/clustered-localization-of-egfrviii-in-glioblastoma-cells-as-detected-by-high-precision-localization-microscopy
#19
Philip S Boyd, Nina Struve, Margund Bach, Jan Philipp Eberle, Martin Gote, Florian Schock, Christoph Cremer, Malte Kriegs, Michael Hausmann
For receptor tyrosine kinases supramolecular organization on the cell membrane is critical for their function. Super-resolution fluorescence microscopy techniques have offered new opportunities for the analysis of single receptor localization. Here, we analysed the cluster formation of the epidermal growth factor receptor variant III (EGFRvIII), a deletion variant which is expressed in glioblastoma. The constitutively activated variant EGFRvIII is expressed in cells with an egfr gene amplification and is thought to enhance the tumorigenic potential especially of glioblastoma cells...
December 28, 2016: Nanoscale
https://www.readbyqxmd.com/read/27825958/simultaneous-blockade-of-interacting-ck2-and-egfr-pathways-by-tumor-targeting-nanobioconjugates-increases-therapeutic-efficacy-against-glioblastoma-multiforme
#20
Szu-Ting Chou, Rameshwar Patil, Anna Galstyan, Pallavi R Gangalum, Webster K Cavenee, Frank B Furnari, Vladimir A Ljubimov, Alexandra Chesnokova, Andrei A Kramerov, Hui Ding, Vida Falahatian, Leila Mashouf, Irving Fox, Keith L Black, Eggehard Holler, Alexander V Ljubimov, Julia Y Ljubimova
Glioblastoma multiforme (GBM) remains the deadliest brain tumor in adults. GBM tumors are also notorious for drug and radiation resistance. To inhibit GBMs more effectively, polymalic acid-based blood-brain barrier crossing nanobioconjugates were synthesized that are delivered to the cytoplasm of cancer cells and specifically inhibit the master regulator serine/threonine protein kinase CK2 and the wild-type/mutated epidermal growth factor receptor (EGFR/EGFRvIII), which are overexpressed in gliomas according to The Cancer Genome Atlas (TCGA) GBM database...
December 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
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